[1] LIU Rong ZHU XiangdongLIU Jiahui WANG Jiahui YANG Xia GAO Yankui LIANG Yonglin,.Role of Bile Acid Receptor in Diabetes and Research Progress of Traditional Chinese Medicine Intervention [J]. Journal of Shaanxi University of Traditional Chinese Medicine, 2024, (05): 1-7. [doi: 10.13424/j.cnki.jsctcm.2024.05.001]
Role of Bile Acid Receptor in Diabetes and Research Progress of Traditional Chinese Medicine Intervention
- Article number:
- 2096-1340(2024)05-0001-07
- Keywords:
- Key words： Diabetes; Bile acids; Traditional Chinese Medicine; Glucose; Lipid
- ZTFLH:
- R587.1
- Code:
- A
- Abstract:
- Abstract： Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels.Its complications are complex and serious.It is difficult to treat DM with western medicine,and its side effects are large.The use of traditional Chinese medicine in the treatment of DM has achieved good results,with stable efficacy,minimal side effects,and the ability to simultaneously prevent and treat complications of DM.In recent years,studies have found that bile acids play an important role in glucose homeostasis,regulating DM glucose and lipid metabolism as well as glucocorticoid secretion.This article discusses the bile acid nuclear receptors Farnesoid X receptor (FXR),Pregnane X receptor (PXR),Vitamin D receptor (VDR),as well as membrane receptors Takeda G protein-coupled receptor 5 (TGR5),Sphingosine-1-phosphate receptor 2 (S1PR2),and muscarinic cholinergic receptor M2 (CHRM2),From the perspective of the correlation between CHRM2 and DM,this study summarizes the relevant research on the treatment of DM by regulating various receptors of bile acids through regulating glucose metabolism,lipid metabolism,insulin secretion,insulin resistance,and inflammation.It also analyzes the possible mechanism of action of traditional Chinese medicine formulas and active ingredients in treating DM by regulating various receptors of bile acids,and proposes that bile acid receptors have a significant impact on obese DM,in order to provide research basis and new ideas for traditional Chinese medicine to treat DM by regulating bile acid receptors.
References:
［1］INTERNATIONAL DIABETES FEDERATION.A new visual identity for the International Diabetes Federation ［Z］.IDF Diabetes Atlas,2021.
［2］陈惠茹,陈珺滢,陈沁.从津液代谢失常论阻塞性睡眠呼吸暂停低通气综合征合并2型糖尿病中医研究进展［J］.陕西中医药大学学报,2019,42(4):129-132.
［3］袁有才,魏光明.新葛根芩连汤对糖尿病大鼠海马ZO-1及JIAM-1蛋白表达的影响［J］.陕西中医药大学学报,2019,42(6):78-79,91.
［4］马淑红,李中南.健脾方对糖尿病大鼠血清B2R、Angptl2及HIF-1α的影响［J］.陕西中医药大学学报,2019,42(5):39-42.
［5］李玫,胡晓晖.参芪地黄汤加减治疗糖尿病肾病的疗效观察［J］.陕西中医药大学学报,2018,41(4):81-82,100.
［6］DONKERS JM,ROSCAM ABBING RLP,VAN DE GRAAF SFJ.Developments in bile salt based therapies:a critical overview［J］.Biochemical Pharmacology,2019,161:1-13.
［7］WAN YJ Y,SHENG LL.Regulation of bile acid receptor activity［J］.Liver Research,2018,2(4):180-185.［8］ZOU WY,LIU BK,WANG YL,et al.Metformin attenuates high glucose-induced injury in islet microvascular endothelial cells［J］.Bioengineered,2022,13(2):4385-4396.
［9］SONNE DP.Mechanisms in endocrinology:FXR signalling:a novel target in metabolic diseases［J］.European Journal of Endocrinology,2021,184(5):R193-R205.
［10］CHIANG JYL,FERRELL JM.Discovery of farnesoid X receptor and its role in bile acid metabolism［J］.Molecular and Cellular Endocrinology,2022,548:111618.
［11］ZHAO T,WANG J,HE AX,et al.Mebhydrolin ameliorates glucose homeostasis in type 2 diabetic mice by functioning as a selective FXR antagonist［J］.Metabolism:Clinical and Experimental,2021,119:154771.
［12］YAN Y,SHA YH,HUANG XZ,et al.Roux-en-Y gastric bypass improves metabolic conditions in association with increased serum bile acids level and hepatic farnesoid X receptor expression in a T2DM rat model［J］.Obesity Surgery,2019,29(9):2912-2922.
［13］XU X,SHI XF,CHEN YD,et al.HS218 as an FXR antagonist suppresses gluconeogenesis by inhibiting FXR binding to PGC-1α promoter［J］.Metabolism:Clinical and Experimental,2018,85:126-138.
［14］HUI SC,LIU Y,CHEN MT,et al.Capsaicin improves glucose tolerance and insulin sensitivity through modulation of the gut microbiota-bile acid-FXR axis in type 2 diabetic db/db mice［J］.Molecular Nutrition & Food Research,2019,63(23):e1900608.
［15］ZHOU Q,SONG N,WANG SQ,et al.Effect of Gegen Qinlian Decoction on hepatic gluconeogenesis in ZDF rats with type 2 diabetes mellitus based on the farnesol X receptor/ceramide signaling pathway regulating mitochondrial metabolism and endoplasmic reticulum stress［J］.Evidence-Based Complementary and Alternative Medicine,2021:9922292.
［16］WU GD,PAN A,ZHANG X,et al.Cordyceps improves obesity and its related inflammation via modulation of Enterococcus cecorum abundance and bile acid metabolism［J］.The American Journal of Chinese Medicine,2022,50(3):817-838.
［17］HUKKANEN J,HAKKOLA J.PXR and 4β-hydroxycholesterol axis and the components of metabolic syndrome［J］.Cells,2020,9(11):2445.
［18］OLADIMEJI PO,CHEN TS.PXR:more than just a master xenobiotic receptor［J］.Molecular Pharmacology,2018,93(2):119-127.
［19］SUN CX,WANG ZP,HU LQ,et al.Targets of statins intervention in LDL-C metabolism:gut microbiota［J］.Frontiers in Cardiovascular Medicine,2022,9:972603.
［20］CHEN K,ZHONG JW,HU L,et al.The role of xenobiotic receptors on hepatic glycolipid metabolism［J］.Current Drug Metabolism,2019,20(1):29-35.
［21］HASSANI-NEZHAD-GASHTI F,RYS J,KUMMU O,et al.Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver［J］.Biochemical Pharmacology,2018,148:253-264.
［22］LIU PH,JIANG L,KONG WM,et al.PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4 α-GLUT2 pathway［J］.Acta Pharmaceutica Sinica B,2022,12(5):2391-2405.
［23］HUKKANEN J,RYSA J,MAKELA KA,et al.The effect of pregnane X receptor agonists on postprandial incretin hormone secretion in rats and humans［J］.Journal of Physiology and Pharmacology:an Official Journal of the Polish Physiological Society,2015,66(6):831-839.
［24］SUN L,SUN ZZ,WANG Q,et al.Role of nuclear receptor PXR in immune cells and inflammatory diseases［J］.Frontiers in Immunology,2022,13:969399.
［25］岳颖,周珺,贾正平,等.影响肝糖代谢的中药活性成分抗糖尿病研究进展［J］.医药导报,2018,37(4):465-469.
［26］刘红,景艳,邹德琴,等.靛玉红衍生物PHⅡ-7通过PXR-CYP3A5/ABCB1信号通路对他克莫司转运及代谢的调节及其作用机制研究［J］.中国药理学通报,2020,36(7):927-934.
［27］杜婧,王少兰,韩曼,等.孕烷X受体与炎症反应及中药干预机制研究进展［J］.陕西中医,2020,41(11):1673-1677.
［28］SASSI F,TAMONE C,D’AMELIO P.Vitamin D:nutrient,hormone,and immunomodulator［J］.Nutrients,2018,10(11):1656.
［29］ROSECRANS R,DOHNAL JC.Seasonal vitamin D changes and the impact on health risk assessment［J］.Clinical Biochemistry,2014,47(7/8):670-672.
［30］RAN YL,HU SY,YU XH,et al.Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus risk in children:a protocol for systematic review and meta-analysis［J］.Medicine,2021,100(28):e26637.
［31］HABIBIAN N,AMOLI MM,ABBASI F,et al.Role of vitamin D and vitamin D receptor gene polymorphisms on residual beta cell function in children with type 1 diabetes mellitus［J］.Pharmacological Reports,2019,71(2):282-288.
［32］MORR M,VIL L,FRANCKHAUSER S,et al.Vitamin D receptor overexpression in β-cells ameliorates diabetes in mice［J］.Diabetes,2020,69(5):927-939.
［33］WEI Z,YOSHIHARA E,HE NH,et al.Vitamin D switches BAF complexes to protect β cells［J］.Cell,2018,173(5):1135-1149.e15.
［34］DONG BN,ZHOU Y,WANG W,et al.Vitamin D receptor activation in liver macrophages ameliorates hepatic inflammation,steatosis,and insulin resistance in mice［J］.Hepatology,2020,71(5):1559-1574.
［35］SHAAT N,KATSAROU A,SHAHIDA B,et al.Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus［J］.PLoS One,2020,15(5):e0232297.
［36］ZHANG DD,CHENG C,WANG Y,et al.The influence of VDR polymorphisms on the type 2 diabetes susceptibility in Chinese:an interaction with hypertriglyceridemia［J］.Molecular Genetics and Genomics,2021,296(4):837-844.
［37］罗丽娅.维生素D通过VDR-PPARγ通路对糖尿病足溃疡组织及巨噬细胞中VDR、PPARγ、VEGFC表达的影响［D］.遵义:遵义医科大学,2021.
［38］ZAKARIA WNA,MOHD YUNUS N,YAACOB NM,et al.Association between vitamin D receptor polymorphisms (BsmI and FokI) and glycemic control among patients with type 2 diabetes［J］.International Journal of Environmental Research and Public Health,2021,18(4):1595.
［39］陈聪,陈家旭,喻嵘,等.左归降糖益肾方对糖尿病肾病MKR鼠肾组织VDR、CYP27B1表达的影响［J］.中华中医药杂志,2019,34(12):5665-5669.
［40］LIU CY,ZHU RY,LIU HX,et al.Aqueous extract of Mori folium exerts bone protective effect through regulation of calcium and redox homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB signaling in diabetic rats［J］.Frontiers in Pharmacology,2018,9:1239.
［41］孙龙.基于VDR/RXR/FGF23信号通路探讨肾元颗粒改善糖尿病肾病小鼠骨代谢的机制［D］.武汉:湖北中医药大学,2021.
［42］曹灵修,任路,张林.中医药防治糖尿病骨质疏松症研究概述［J］.山东中医杂志,2020,39(5):525-529.
［43］贾维中.加味骨痛仙胶囊对DM大鼠模型骨密度、VDR-mRNA影响的实验研究［D］.哈尔滨:黑龙江中医药大学,2007.
［44］PORTINCASA P,DI CIAULA A,GARRUTI G,et al.Bile acids and GPBAR-1:dynamic interaction involving genes,environment and gut microbiome［J］.Nutrients,2020,12(12):3709.
［45］TU J,WANG YM,JIN LH,et al.Bile acids,gut microbiota and metabolic surgery［J］.Frontiers in Endocrinology,2022,13:929530.
［46］KUMAR DP,ASGHARPOUR A,MIRSHAHI F,et al.Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet α cells to promote glucose homeostasis［J］.The Journal of Biological Chemistry,2016,291(13):6626-6640.
［47］SHAPIRO H,KOLODZIEJCZYK AA,HALSTUCH D,et al.Bile acids in glucose metabolism in health and disease［J］.The Journal of Experimental Medicine,2018,215(2):383-396.
［48］CHEN YS,LIU HM,LEE TY.Ursodeoxycholic acid regulates hepatic energy homeostasis and white adipose tissue macrophages polarization in leptin-deficiency obese mice［J］.Cells,2019,8(3):253.
［49］HUANG SL,MA SY,NING MM,et al.TGR5 agonist ameliorates insulin resistance in the skeletal muscles and improves glucose homeostasis in diabetic mice［J］.Metabolism:Clinical and Experimental,2019,99:45-56.
［50］HUI SC,HUANG L,WANG XL,et al.Capsaicin improves glucose homeostasis by enhancing glucagon-like peptide-1 secretion through the regulation of bile acid metabolism via the remodeling of the gut microbiota in male mice［J］.FASEB Journal:Official Publication of the Federation of American Societies for Experimental Biology,2020,34(6):8558-8573.
［51］WANG Z,LI XL,HONG KF,et al.Total flavonoids of Astragalus ameliorated bile acid metabolism dysfunction in diabetes mellitus［J］.Evidence-Based Complementary and Alternative Medicine,2021:6675567.
［52］穆国华.黄连-肉桂治疗T2DM的临床应用及对基于肠道菌群的BA/TGR5/GLP-1通路影响［D］.北京:北京中医药大学,2021.
［53］WANG LY,CHENG KC,LI YX,et al.Glycyrrhizic acid increases glucagon like peptide-1 secretion via TGR5 activation in type 1-like diabetic rats［J］.Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie,2017,95:599-604.
［54］CHEN H,YAO Y,WANG WB,et al.Ge-gen-Jiao-Tai-wan affects type 2 diabetic rats by regulating gut microbiota and primary bile acids［J］.Evidence-Based Complementary and Alternative Medicine,2021:5585952.
［55］WENG ZB,CHEN YR,LV JT,et al.A review of bile acid metabolism and signaling in cognitive dysfunction-related diseases［J］.Oxidative Medicine and Cellular Longevity,2022:4289383.
［56］HE YZ,SHI BY,ZHAO XR,et al.Sphingosine-1-phosphate induces islet β-cell proliferation and decreases cell apoptosis in high-fat diet/streptozotocin diabetic mice［J］.Experimental and Therapeutic Medicine,2019,18(5):3415-3424.
［57］ZHAO L,XUAN ZF,SONG WF,et al.A novel role for farnesoid X receptor in the bile acid-mediated intestinal glucose homeostasis［J］.Journal of Cellular and Molecular Medicine,2020,24(21):12848-12861.
［58］KITADA Y,KAJITA K,TAGUCHI K,et al.Blockade of sphingosine 1-phosphate receptor 2 signaling attenuates high-fat diet-induced adipocyte hypertrophy and systemic glucose intolerance in mice［J］.Endocrinology,2016,157(5):1839-1851.
［59］GUAN BY,TONG JL,HAO HP,et al.Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases［J］.Acta Pharmaceutica Sinica B,2022,12(5):2129-2149.
［60］YANG YY,ZHAO QY.Exenatide regulates inflammation and the production of reactive oxygen species via inhibition of S1PR2 synthesis［J］.Advances in Clinical and Experimental Medicine:Official Organ Wroclaw Medical University,2021,30(5):555-561.
［61］CHEN W,XIANG H,CHEN RF,et al.S1PR2 antagonist ameliorate high glucose-induced fission and dysfunction of mitochondria in HRGECs via regulating ROCK1［J］.BMC Nephrology,2019,20(1):135.
［62］SERAFIMIDIS I,RODRIGUEZ-AZNAR E,LESCHE M,et al.Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling［J］.PLoS Biology,2017,15(3):e2000949.
［63］LIU K,SUN TT,LUAN Y,et al.Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways［J］.Andrology,2022,10(2):404-418.
［64］张雨寒,罗凤鸣.慢性阻塞性肺疾病与毒蕈碱型胆碱能受体［J］.中国呼吸与危重监护杂志,2021,20(9):673-676.
［65］JEONG SW,CHUNG M,PARK SJ,et al.Genome-wide association study of metabolic syndrome in koreans［J］.Genomics & Informatics,2014,12(4):187-194.
［66］DIMITRIADIS F,PAPAIOANNOU M,SOKOLAKIS I,et al.The effect of low-intensity extracorporeal shockwave treatment on the urinary bladder in an experimental diabetic rat model［J］.International Neurourology Journal,2021,25(1):34-41.
Memo
基金项目：宁夏回族自治区重点研发计划项目（2022CMG02034）;甘肃省教育厅产业支撑计划项目（2021CYZC-03）